Implementing narrow banding imaging with dual focus magnification for histological prediction of small rectosigmoid polyps in Vietnamese setting

Abstract Background and Aim Small rectosigmoid colorectal polyps (<10 mm) are prevalent, with a low prevalence of advanced neoplastic lesions. The “diagnose‐and‐leave” strategy, employing narrow band imaging (NBI), is gaining popularity for its safety and cost‐effectiveness by reducing polypectomy complications and minimizing histopathology expenses. This study assessed the diagnostic efficacy of NBI with dual focus (DF) magnification for real‐time neoplastic prediction of rectosigmoid polyps and explored the feasibility of implementing this strategy in Vietnam. Methods In a prospective single‐center study, 307 rectosigmoid polyps from 245 patients were analyzed using three consecutive endoscopic modes: white light endoscopy (WLE), NBI, and NBI‐DF. Endoscopists assessed polyps for size, location, macroscopic shape, optical diagnosis, and confidence levels before histopathological evaluation. High confidence was assigned when the polyp exhibited all features of a single histology type. Predictions were compared with final histopathology results. Results Of the total, 237 (77.2%) were diminutive (≤5 mm) polyps, and 18 (5.8%) were advanced neoplastic lesions. WLE + NBI and WLE + NBI + NBI‐DF exhibited significantly higher accuracy compared to WLE (88.6% and 90.2% vs 74.2%, P < 0.01). For diminutive polyps, the DF mode significantly increased the rate of high‐confidence optical diagnoses (89.1% vs 94.9%, P < 0.001). WLE + NBI + NBI‐DF demonstrated high sensitivity (90.1%), specificity (95.5%), and negative predictive value (93.4%) in high‐confidence predictions, enabling the implementation of the “diagnose‐and‐leave” strategy. This approach would have reduced 58.2% of unnecessary polypectomies without missing any advanced neoplastic lesions. Conclusion NBI and DF modes provide accurate neoplastic predictions for rectosigmoid polyps. For diminutive polyps, DF magnification improves the confidence level of the optical diagnosis, allowing the safe implementation of the “diagnose‐and‐leave” strategy.


Introduction
The application of white light endoscopy (WLE) in isolation is inadequate for discriminating between neoplastic and nonneoplastic polyps, which may lead to unnecessary excision of many lesions.Enhanced imaging endoscopy has been recognized as advantageous for assessing colorectal polyps, with real-time optical diagnosis gaining increasing acceptance and endorsement by guidelines. 1 Given the low likelihood of high-risk lesions in the rectosigmoid segment, a recent novel approach, "diagnoseand-leave," is being demonstrated as a potentially cost-effective strategy for managing rectosigmoid polyps.2][3] Furthermore, the application of this approach should be contingent on an optical diagnosis meeting the accuracy thresholds prescribed by the Preservation and Incorporation of Valuable Endoscopic Innovation document, as outlined by the American Society of Gastrointestinal Endoscopy (ASGE) and the European Society of Gastrointestinal Endoscopy (ESGE). 1,4The "diagnose-and-leave" strategy for diminutive (≤ 5 mm) colorectal lesions is clinically acceptable if real-time colonoscopy can achieve at least 90% sensitivity and 80% specificity (ESGE) and a negative predictive value (NPV) of at least 90% (ASGE) for high-confidence endoscopic prediction of diminutive colorectal neoplasia in the rectosigmoid region, with histopathology serving as the gold standard. 1,5Recently, an innovative endoscopic system with novel features, such as narrow band imaging (NBI) and dual focus (DF) magnification mode, has been introduced.This system allows users to adjust magnification for close-up examination easily.With this optical advancement, users can choose between two focus settings, achieving a 45-fold magnification on a 26-inch monitor.Furthermore, by utilizing a 1.4-to 2.0-fold electronic zoom function, a maximum magnification of 90-fold can be attained. 6,7][9][10][11][12] While these advanced diagnostic techniques are gaining popularity in Vietnam, more systematic data on their perfomance in predicting colorectal polyp histology are needed.Our previous study demonstrated the high diagnostic yield of NBI-DF for small colorectal polyps. 13Therefore, we performed a further study to assess the diagnostic yield of NBI and NBI-DF for predicting small rectosigmoid neoplastic polyps and the feasibility of employing the "diagnose-and-leave" strategy.

Methods
Study design, setting, and patient recruitment.This cross-sectional, single-center observational study was conducted at the City General Hospital in Ho Chi Minh City, Vietnam, from September 2020 to May 2021.We gathered data, building upon the findings of a previous study, with a more focused emphasis on the rectosigmoid colon. 13The study's inclusion criteria consisted of the following: (1) individuals aged 18 years and above who underwent elective colonoscopy (screening, surveillance, or diagnostic workup) in consecutive order, having provided informed consent before participation; (2) detection of small colorectal polyps (<10 mm in size) in the rectosigmoid colon; and (3) retrieval of polyps for histological examination.Exclusion criteria included: (1) individuals with polyps larger than 10 mm or located outside the rectosigmoid colon; (2) those with suboptimal bowel preparation, indicated by  a Boston Bowel Preparation Scale score less than 6 and incomplete cecal intubation; (3) individuals with contraindications to total colonoscopies, such as severe heart failure, severe respiratory failure, shock, or similar conditions; and (4) individuals diagnosed with synchronous colorectal cancer, inflammatory bowel disease, polyposis syndrome, or pregnancy.
Data collection.Patient demographic data, including age and gender, were collected.
To prepare for the colonoscopic procedures, each patient ingested 1.5-2 L of polyethylene glycol solution and 1000 mg of simethicone.Colonoscopies were performed by two experienced endoscopists (QDL and NQL) who had previously conducted more than 1000 procedures using the NBI and DF modes.The evaluation utilized the Olympus EVIS EXERA III series 190, which features NBI endoscopy in DF mode, a light source, image processing, and a flexible colonoscope.A push-button system enabled seamless switching between NBI and WLE.The NBI-DF mode employed a 1.4Â electronic zoom and a transparent cap for precise focus.
Colonoscopies were performed using WLE for the entire colon, with the endoscope inserted into the Bauhin valve and the ileocecal angle.During endoscopic tube withdrawal, the endoscopists closely observed the small rectosigmoid colorectal polyps.In the WLE mode, QDL and NQL assess the polyp according to the number, location, size (compared to the open jaws of the biopsy forceps or snare), gross morphology according to the Paris classification, and histological prediction. 14Lesion size was assessed by comparing the polyp dimensions to those of the biopsy forceps (2.3 mm closed, ENDO-FLEX) and polypectomy snare (10 mm open, SnareMaster ® , Olympus).Based on previous reports, polyps were classified as either nonneoplastic or neoplastic based on their surface patterns: polyps were classified as either nonneoplastic (circular white pits, very fine capillary network bordering the pit) or neoplastic (circular/ oval/linear/cerebri form pits, dendrite or gyrus-like pits, or an irregular arrangement or loss of pits). 15Subsequently, the polyp was examined in NBI mode and NBI-DF mode using the NICE classification to classify the rectal polyp based on its color, blood vessels, and surface characteristics (Table S1, Supporting information). 10Afterward, the endoscopist assessed the confidence of the prediction results as either low or high.If the polyp exhibits all the features of a single histology type, the prediction was deemed to have "high confidence."Any uncertainty or doubt about any feature results in a prediction with low confidence. 5n independent observer (TMH) recorded the diagnosis at each stage.A simethicone-based washing system was used during the endoscopy to enhance foam dissolution and surface cleaning, improving the assessment process.All polyps were removed en bloc through snare polypectomy or biopsy and sent for histological evaluation.In cases of multiple rectal lesions with NICE type 1 suspected to be hyperplastic, endoscopists were not obligated to remove all of them.Instead, they selectively removed or sampled only the first five, prioritizing the largest lesions.The procedure was illustrated through Video S1 and Figures 1 and 2.
Histopathological investigations.After resection, each lesion was collected in individually numbered containers.The specimens were stained with standard hematoxylin and eosin (H&E) and analyzed by an expert gastrointestinal pathologist (HML) blinded to all the endoscopic images and assessments.Lesions were categorized based on the 2019 World Health Organization (WHO) classification. 15Neoplastic lesions were classified as adenomas, sessile serrated lesions (SSLs), or adenomatous polyps, while nonneoplastic lesions were classified as inflammatory polyps, hyperplastic polyps, or normal colorectal mucosa.High-risk neoplastic lesions included high-risk adenomas with villous components and SSLs with dysplasia.
Statistical analysis.This study aimed to assess the accuracy of optical diagnosis for predicting neoplastic lesions in the rectum and sigmoid via comparison with histopathology, which is considered the reference standard.The visual diagnosis was evaluated by creating 2 Â 2 contingency tables to calculate sensitivity, specificity, predictive values, and their corresponding 95% confidence intervals (CIs).Categorical variables are expressed as proportions or percentages, and continuous variables are presented as means (AE standard deviation, SD).Paired proportions were compared using McNemar's test, with statistical significance set at P < 0.05 (two-sided).SPSS statistical software       2).Within the subset of neoplastic polyps, 12.1% were erroneously categorized as NICE type 1 when using WLE + NBI and 8.2% when applying WLE + NBI + NBI-DF.Similarly, among the nonneoplastic polyps, 10.6% were misidentified as NICE 2 under WLE + NBI, and 11.3% were misidentified under WLE + NBI + NBI-DF.The greatest agreement was observed between histopathology and the prediction based on WLE + NBI + NBI-DF (91.2%, kappa = 0.823), followed by WLE and NBI (89.6%, kappa = 0.791).The lowest agreement was found with WLE alone (63.2%, kappa = 0.272).The clinicopathological features of 18 high-risk lesions are shown in Table S2.Notably, all highrisk lesions were accurately classified as NICE 2 and made with high confidence.
Diagnostic yield of WLE + NBI and WLE + NBI + NBI-DF for characterizing histological lesions in the rectosigmoid colon according to polyp size with high confidence.Tables 4 and 5 present an overview of the optical diagnostic performance and the rate of high confidence stratified by polyp size.
Regarding the confidence level, in the 6-9 mm group, adding the DF mode did not significantly improve the confidence rate (94.3 vs 97.1, P = 0.5).In addition, for diminutive polyps, the DF mode significantly improved the proportion of highconfidence optical diagnoses (89.1% vs 94.9%, P < 0.001).
WLE + NBI and WLE + NBI + NBI-DF met the ASGE recommendation, with an NPV > 90% for predicting neoplastic polyps.However, for the ESGE recommendation, only WLE + NBI + NBI-DF achieved a sensitivity >90% and specificity >80% in predicting neoplastic polyps.We devised the subsequent flowchart to document the implementation of the "diagnose and leave" strategy using NBI-DF, as it meets the ASGE and ESGE guidelines (Fig. 3).When implemented, this approach led to the removal of 99 out of 237 (41.8%) polyps with low confidence (11 polyps) or those predicted as neoplastic lesions (87 lesions).Additionally, in 10 out of 98 (10.2%) polyps, neoplastic lesions were misdiagnosed, including nine low-grade tubular adenomas and one SSL.However, with the implementation of this strategy, no high-risk lesions could be missed.

Discussion
To the best of our knowledge, our study is the first to investigate the utility of NBI and DF magnification for real-time neoplastic histology prediction of small rectosigmoid polyps in the Vietnamese population.We also evaluated the feasibility of adopting the "diagnose-and-leave" strategy following recommendations from the ASGE and ESGE.First, we reaffirmed the effectiveness of WLE + NBI and WLE + NBI + NBI-DF in predicting neoplastic histopathology of rectosigmoid polyps  8,11,16 The difference in our study is that we employed consecutive three-step evaluations in real time with our local team in the Vietnamese setting.The remarkable outcomes in this study were attributable to a combination of critical factors, including (1) novel enhanced endoscopy with easy-to-use magnification mode, (2) a well-skilled endoscopist who had more than 10 years of experience, (2) excellent bowel preparation with intensive polyp surface cleaning before prediction, and (3) universal and well-compatible, easy-to-use classification (NICE classification). 13Furthermore, the addition of the DF mode improved the performance compared to NBI alone in sensitivity (89.8 vs 93.6, P = 0.13) and accuracy (88.6 vs 90.2, P = 0.13), but this difference was not statistically significant (P = 0.13).Thus, regarding small neoplastic prediction, WLE + NBI may be considered noninferior to NBI-DF in the rectosigmoid segment.This nonsignificant improvement could be due to the endoscopist's expertise or limitations in magnification (approximately Â65) compared to other colonoscopies (Â100 to Â100-125).Additionally, the 190 series may offer optical information or additional details that may lead to interpretation confusion. 17owever, regarding the level of confidence, adding the DF mode aided endoscopists in lesion characterization and a notable increase in the percentage of high-confidence interpretations for polyp histology, even for polyps measuring ≤5 mm, rising from 89.1% with NBI alone to 94.9% with NBI + NBI-DF (P < 0.001; Table 4 and Fig. 5).
Prior studies have demonstrated that the use of DF mode or magnifying endoscopy can improve the rate of highconfidence optical diagnosis. 8,18The improvement in confidence level was due to magnification (65Â) coupled with increased resolving power (1.56Â) in the near-focus view and the prefreeze function, which identifies the sharpest image from the earlier 4-29 frames.These factors led to fewer image capture attempts for high-quality photos and higher subjective image quality scores. 17egarding the feasibility of the "diagnose-and-leave" strategy, we analyzed 6-9 mm and 5 mm group sizes.In the 6-9 mm group, WLE + NBI + NBI-DF met the ASGE's NPV threshold but did not satisfy the ESGE criteria and had a modest 5.7% reduction in polypectomies.Additionally, for diminutive polyps, WLE + NBI + NBI-DF met the stringent criteria of both ESGE and ASGE, demonstrating a substantial overall reduction of 58.9%.Among the 237 diminutive rectosigmoid lesions evaluated with high confidence, only 11 were incorrectly identified as nonneoplastic lesions: 9 were TA-LGDs, and one non-dysplastic SSL.
Similarly, previous studies have demonstrated that both NBI and NBI-DF can meet the criteria of ASGE or ESGE 7,8,19 (Table 6).Additionally, the meeting of ASGE and ESGE thresholds of WLE + NBI + NBI-DF may be due to the improvement of the rate of high-confidence lesions in optical diagnosis.
Furthermore, the limitation of the NICE classification was that hyperplastic polyps and SSLs could not be differentiated within the NICE 1 category.However, we did not use the Workgroup Serrated Polyps and Polyposis classification due to the low proportion of SSL (1.3%).In the rectosigmoid colon, the proportion of NICE type 1 lesions ranging from 1 to 5 mm of SSL is less than 2%, indicating that the NPV of NICE type 1 features for both adenoma and SSL is high. 20The sole distinguishing feature within the NICE classification between these two types is the presence of large open pits in the SSL.However, the DF mode may facilitate this differentiation (Fig. 6).
The misclassification could also be related to endoscopistrelated factors, such as poor photo documentation, limitations in classification systems, and incomplete histology.In real-time, photo documentation can be rendered by a bowel movement, the experience of an endoscopist.Furthermore, some adenomas are mistakenly classified based on an initial assessment of color, similar to the background mucosa under WLE and NBI. 21Furthermore, 15% of lesions measuring 1-3 mm, identified as adenomas under NBI, are pathologically diagnosed as normal tissue, regardless of the removal method (snaring or forceps), revealing a discrepancy between endoscopic and pathological assessments. 22However, we did not assess the accuracy of our pathologists; therefore, the effect on the outcome due to variation in pathological diagnosis accuracy could not be assessed.This study's prospective data collection and real-time optical diagnosis have significant implications for clinical practice.The NBI and DF models demonstrate promising potential for accurately identifying and excluding diminutive neoplastic rectosigmoid lesions, supporting the adoption of the "diagnoseand-leave" strategy.This approach can effectively reduce procedural risks and pathological costs, diverging from the costly practice of biopsying or resecting all lesions.However, successfully implementing this strategy requires standardized training, accreditation, patient acceptance, and the availability of endoscopy systems.Moreover, introducing optical diagnosis to endoscopists accustomed to WLE presents a challenge.Concerns such as legal liability and financial disincentives may hinder its adoption.Nevertheless, inclusion in clinical guidelines and developing a reimbursement strategy could facilitate its integration into clinical practice.
Our study has several limitations.First, in our study, the lower limit value of NPV and sensitivity (95% CI) did not meet the threshold, which were partially due to our small sample size and a lower prevalence of non-neoplastic cases as multiple hyperplastic lesions were not resected due to ethical concerns.To obtain more comprehensive insights, conducting more extensive, multicenter studies involving a broader range of less experienced and community physicians with a larger sample size is imperative.Second, the study did not assess individual patient risk or the proportion of patients with serrated adenomas or their associated risks due to the limitations of the NICE classification system, which potentially impacts the predictive outcome.Third, all procedures were conducted by a single expert, potentially limiting generalizability.We typically follow consecutive phases in our daily practice, including WLE, NBI, and NBI-DF.Additionally, we did not opt for randomized controlled trials.Furthermore, we did not compare our findings with those of WLE with DF magnification (WLE-DF) due to the absence of a validated classification system for predicting polyp histology using white light.Finally, the "resect and discard" strategy was excluded due to legal requirements, the absence of a Vietnamese surveillance interval policy, or the common occurrence of early colorectal cancers in the rectosigmoid.
In summary, our study underscores the excellent diagnostic performance of both NBI and NBI-DF for small neoplastic polyps in the rectosigmoid segment.Adopting the "diagnoseand-leave" strategy with NBI-DF can significantly decrease unnecessary procedures and associated costs by up to 58.2% without compromising the detection of high-risk lesions.This approach is especially beneficial in low-resource settings such as Vietnam, where traditional optical zoom techniques may be constrained.

Figure 1 A
Figure 1 A sigmoid colon lesion (4 mm, 0-Is) in WLE (a) was classified as NICE type 1 in the WLE+ NBI and WLE + NBI + NBI-DF modes and was characterized by pale color, absence of vessels, and a black dot pattern (b, c).Histopathology: hyperplastic polyp.

Figure 2 A
Figure 2 A rectal lesion (5 mm, 0-Is) was detected via WLE (a).It is classified as NICE type 2 in NBI and NBI-DF modes.It is characterized by a brown color and thick brown vessels surrounding tubular, oval, or pentagonal pits (b, c).Histopathology revealed a low-grade tubular adenoma.

Figure 5 ATable 6
Figure 5 A lesion (5 mm, 0-Is) in the sigmoid colon was initially identified as neoplastic in WLE and NICE type 2 patients with low confidence in NBI mode.However, with the application of dual focus mode, the lesion was confidently classified as NICE type 2 (C).Histopathology revealed a low-grade tubular adenoma.

Figure 6 A
Figure 6 A lesion (3 mm, 0-IIa) in the sigmoid colon.Initially, the lesions were classified as nonneoplastic according to the WLE mode (A) or NICE type 1 according to the NBI and NBI-DF modes.A large open pit, a hallmark of serrated lesions, was evident in the NBI-DF images.The confirmed histopathology was a sessile serrated lesion.

Table 1
Clinical characteristics of the patients and polyps ResultsPatient clinical and pathological profile characteristics.From August 2020 to May 2021, 324 polyps were collected from 245 consecutive patients who met the sample selection criteria.Histopathological examination was lesions measuring less than ≤5 mm and 6-9 mm in size accounted for 49.1% (213/307 polyps) and 78.1% (82/307 polyps) of the patients, respectively.Notably, no cases of cancer were detected.

Table 2
Association between endoscopic neoplastic prediction and histological findings